The purpose of this work is to define the cellular and molecular mechanism of the hemoglobin switch which occurs in sheep and goats in response to high concentrations of erythropoietin. Current efforts are focused on defining the precise stage in erythropoiesis at which the switch is regulated and specifically determining whether this occurs before or simultaneously with the onset development is being defined. The effect of erythropoietin on synthesis of the individual globins is being studied in hepatic and bone marrow cells of fetuses at various times of gestation. The types of hemoglobin synthesized in individual erythroid colonies in vitro is under investigation in an effort to determine whether erythropoietin mediates the switch by intracellular modulation of expression of the individual globin genes or by selection among various precursor cells which have been predetermined as to which globin genes their progeny will express. es and c